Altered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice.

TitleAltered circadian and homeostatic sleep regulation in prokineticin 2-deficient mice.
Publication TypeJournal Article
Year of Publication2007
AuthorsHu W-P, Da Li J-, Zhang C, Boehmer L, Siegel JM, Zhou Q-Y
Date Published2007 Mar
KeywordsAnimals, Arousal, Circadian Rhythm, Electroencephalography, Electromyography, Gastrointestinal Hormones, Homeostasis, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuropeptides, Sleep Deprivation, Sleep Stages, Social Environment, Suprachiasmatic Nucleus, Wakefulness

STUDY OBJECTIVES: Sleep is regulated by circadian and homeostatic processes. Recent studies with mutant mice have indicated that circadian-related genes regulate sleep amount, as well as the timing of sleep. Thus a direct link between circadian and homeostatic regulation of sleep may exist, at least at the molecular level. Prokineticin 2 (PK2), which oscillates daily with high amplitude in the suprachiasmatic nuclei (SCN), has been postulated to be an SCN output molecule. In particular, mice lacking the PK2 gene (PK2-/-) have been shown to display significantly reduced rhythmicity for a variety of circadian physiological and behavioral parameters. We investigated the role of PK2 in sleep regulation.

DESIGN: EEG/EMG sleep-wake patterns were recorded in PK2-/- mice and their wild-type littermate controls under baseline and challenged conditions.

MEASUREMENTS AND RESULTS: PK2-/- mice exhibited reduced total sleep time under entrained light-dark and constant darkness conditions. The reduced sleep time in PK2-/- mice occurred predominantly during the light period and was entirely due to a decrease in non-rapid eye movement (NREM) sleep time. However, PK2-/- mice showed increased rapid eye movement (REM) sleep time in both light and dark periods. After sleep deprivation, compensatory rebound in NREM sleep, REM sleep, and EEG delta power was attenuated in PK2-/- mice. In addition, PK2-/- mice had an impaired response to sleep disturbance caused by cage change in the light phase.

CONCLUSIONS: These results indicate that PK2 plays roles in both circadian and homeostatic regulation of sleep. PK2 may also be involved in maintaining the awake state in the presence of behavioral challenges.

Alternate JournalSleep
PubMed ID17425220
PubMed Central IDPMC2673012
Grant ListR01 MH067753-05 / MH / NIMH NIH HHS / United States